tbuckley/cabot-search huggingface dataset:
Icenticaftor, a CFTR Potentiator, in COPD: A Multicenter, Parallel-Group, Double-Blind Clinical Trial
Authors: Fernando J. Martinez, Gerard J. Criner, Christian Gessner, Margret Jandl, Fernando Scherbovsky, Masaharu Shinkai, Thomas M. Siler, Claus F. Vogelmeier, Robert Voves, Jadwiga A. Wedzicha, Christian Bartels, Ivan Bottoli, Stuart Byiers, Pamela Cardenas, Joerg H. Eckert, Florian S. Gutzwiller, Barbara Knorr, Mahavir Kothari, Rutvick Parlikar, Ana-Maria Tanase, Frits M.E. Franssen
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction is associated with mucus accumulation and worsening chronic obstructive pulmonary disease (COPD) symptoms. Objectives: The aim of this phase IIb dose-finding study was to compare a CFTR potentiator, icenticaftor (QBW251), with placebo in patients with COPD and chronic bronchitis. Methods: Patients with COPD on triple therapy for at least three months were randomized to six treatment arms (icenticaftor 450, 300, 150, 75, or 25 mg or placebo twice daily [b.i.d.]) in a 24-week, multicenter, parallel-group, double-blind study. The primary endpoint was change from baseline in trough FEV1 after 12 weeks. Secondary endpoints included change from baseline in trough FEV1 and Evaluating Respiratory Symptoms in COPD (E-RS) total and cough and sputum scores after 24 weeks. Multiple comparison procedure-modeling was conducted to characterize dose–response relationship. Rescue medication use, exacerbations, and change in serum fibrinogen concentration after 24 weeks were assessed in exploratory and post hoc analyses, respectively. Measurements and Main Results: Nine hundred seventy-four patients were randomized. After 12 weeks of icenticaftor treatment, no dose–response relationship for change from baseline in trough FEV1 was observed; however, it was observed for E-RS cough and sputum score. A dose–response relationship was observed after 24 weeks for trough FEV1, E-RS cough and sputum and total scores, rescue medication use, and fibrinogen. A dose of 300 mg b.i.d. was consistently the most effective. Improvements for 300 mg b.i.d. versus placebo were also seen in pairwise comparisons of these endpoints. All treatments were well tolerated. Conclusions: The primary endpoint was negative, as icenticaftor did not improve trough FEV1 over 12 weeks. Although the findings must be interpreted with caution, icenticaftor improved trough FEV1; reduced cough, sputum, and rescue medication use; and lowered fibrinogen concentrations at 24 weeks. Clinical trial registered with www.clinicaltrials.gov (NCT 04072887).
First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study
Authors: Siow Ming Lee, Christian Schulz, Kumar Prabhash, Dariusz Kowalski, Aleksandra Szczesna, Baohui Han, Achim Rittmeyer, Toby Talbot, David Vicente, Raffaele Califano, Diego Cortinovis, Anh Tuan Le, Dingzhi Huang, Geoffrey Liu, Federico Cappuzzo, Jessica Reyes Contreras, Martin Reck, Ramon Palmero, Milena Perez Mak, Youyou Hu, Stefanie Morris, Elen Höglander, Mary Connors, Alice M Biggane, Hans Kristian Vollan, Solange Peters
Journal: The Lancet (2023)
Assessment of Preserved Ratio Impaired Spirometry Using Pre- and Post-Bronchodilator Spirometry in a Randomly Sampled Symptomatic Cohort
Authors: Kate M. A. Magner, Mathew Cherian, G. A. Whitmore, Katherine L. Vandemheen, Celine Bergeron, Andreanne Cote, Stephen K. Field, Catherine Lemière, R. Andrew McIvor, Shawn D. Aaron
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Assessment of Preserved Ratio Impaired Spirometry Using Pre- and Post-Bronchodilator Spirometry in a Randomly Sampled Symptomatic Cohort." American Journal of Respiratory and Critical Care Medicine, 208(10), pp. 1129–1131
What we know and don’t know about the health and social care workforce
Authors: Tara Lamont, Cat Chatfield, Kieran Walshe
Journal: BMJ (2023)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following What we know and don’t know about the health and social care workforce Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Ongoing Rapid Evolution of a Post-Y Region Revealed by Chromosome-Scale Genome Assembly of a Hexaploid Monoecious Persimmon (<i>Diospyros kaki</i>)
Authors: Ayano Horiuchi, Kanae Masuda, Kenta Shirasawa, Noriyuki Onoue, Naoko Fujita, Koichiro Ushijima, Takashi Akagi
Journal: Molecular Biology and Evolution (2023)

Plants have evolved sex chromosomes independently in many lineages, and loss of separate sexes can also occur. In this study, we assembled a monoecious recently hexaploidized persimmon (Diospyros kaki), in which the Y chromosome has lost the maleness-determining function. Comparative genomic analysis of D. kaki and its dioecious relatives uncovered the evolutionary process by which the nonfunctional Y chromosome (or Ymonoecy) was derived, which involved silencing of the sex-determining gene, OGI, approximately 2 million years ago. Analyses of the entire X and Ymonoecy chromosomes suggested that D. kaki's nonfunctional male-specific region of the Y chromosome (MSY), which we call a post-MSY, has conserved some characteristics of the original functional MSY. Specifically, comparing the functional MSY in Diospyros lotus and the nonfunctional "post-MSY" in D. kaki indicated that both have been rapidly rearranged, mainly via ongoing transposable element bursts, resembling structural changes often detected in Y-linked regions, some of which can enlarge the nonrecombining regions. The recent evolution of the post-MSY (and possibly also MSYs in dioecious Diospyros species) therefore probably reflects these regions' ancestral location in a pericentromeric region, rather than the presence of male-determining genes and/or genes controlling sexually dimorphic traits.
Alcohol Consumption and Risk of Stroke: A Meta-analysis—Correction
Authors: Michael Steinman, C Landefeld, San Francisco, Ralph Gonzales
Journal: JAMA (2003)

Kristi Reynolds, MPH; Brian Lewis, MPH; John David L. Nolen, MD, PhD, MSPH; Gregory L. Kinney, MPH; Bhavani Sathya, MPH; Jiang He, MD, PhD
Effect of the methotrexate discontinuation for 1 versus 2 weeks on vaccine response to seasonal influenza vaccine in rheumatoid arthritis: a noninferiority randomized controlled trial
Authors: Jin Kyun Park, Yun Jong Lee, Eun Ha Kang, Kichul Shin, Min Jung Kim, You‐Jung Ha, Se Rim Choi, Jun Won Park, Mi Hyeon Kim, Ju Yeon Kim, Ji In Jung, Yunhee Choi, Kevin L. Winthrop, Eun Bong Lee
Journal: Arthritis & Rheumatology (2023)

Disclosure form Appendix S1: Supplementary Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
<scp>IĸB</scp> Protein <scp>BCL3</scp> as a Controller of Osteogenesis and Bone Health
Authors: Hussain Jaffery, Carmen Huesa, Sabarinadh Chilaka, John Cole, James Doonan, Moeed Akbar, Lynette Dunning, Kathleen Elizabeth Tanner, Rob J. van ‘t Hof, Iain B. McInnes, Ruaidhrí J. Carmody, Carl S. Goodyear
Journal: Arthritis & Rheumatology (2023)

Objective IĸB protein B cell lymphoma 3‐encoded protein (BCL3) is a regulator of the NF‐κB family of transcription factors. NF‐κB signaling fundamentally influences the fate of bone‐forming osteoblasts and bone‐resorbing osteoclasts, but the role of BCL3 in bone biology has not been investigated. The objective of this study was to evaluate BCL3 in skeletal development, maintenance, and osteoarthritic pathology. Methods To assess the contribution of BCL3 to skeletal homeostasis, neonatal mice (n = 6–14) lacking BCL3 ( Bcl3 −/− ) and wild‐type (WT) controls were characterized for bone phenotype and density. To reveal the contribution to bone phenotype by the osteoblast compartment in Bcl3 −/− mice, transcriptomic analysis of early osteogenic differentiation and cellular function (n = 3–7) were assessed. Osteoclast differentiation and function in Bcl3 −/− mice (n = 3–5) was assessed. Adult 20‐week Bcl3 −/− and WT mice bone phenotype, strength, and turnover were assessed. A destabilization of the medial meniscus model of osteoarthritic osteophytogenesis was used to understand adult bone formation in Bcl3 −/− mice (n = 11–13). Results Evaluation of Bcl3 −/− mice revealed congenitally increased bone density, long bone dwarfism, increased bone biomechanical strength, and altered bone turnover. Molecular and cellular characterization of mesenchymal precursors showed that Bcl3 −/− cells displayed an accelerated osteogenic transcriptional profile that led to enhanced differentiation into osteoblasts with increased functional activity, which could be reversed with a mimetic peptide. In a model of osteoarthritis‐induced osteophytogenesis, Bcl3 −/− mice exhibited decreased pathological osteophyte formation ( P &lt; 0.05). Conclusion Cumulatively, these findings demonstrate that BCL3 controls developmental mineralization to enable appropriate bone formation, whereas in a pathological setting, it contributes to skeletal pathology. image
Resistance training prescription for muscle strength and hypertrophy in healthy adults: a systematic review and Bayesian network meta-analysis
Authors: Brad S Currier, Jonathan C Mcleod, Laura Banfield, Joseph Beyene, Nicky J Welton, Alysha C D'Souza, Joshua A J Keogh, Lydia Lin, Giulia Coletta, Antony Yang, Lauren Colenso-Semple, Kyle J Lau, Alexandria Verboom, Stuart M Phillips
Journal: British Journal of Sports Medicine (2023)

Objective To determine how distinct combinations of resistance training prescription (RTx) variables (load, sets and frequency) affect muscle strength and hypertrophy. Data sources MEDLINE, Embase, Emcare, SPORTDiscus, CINAHL, and Web of Science were searched until February 2022. Eligibility criteria Randomised trials that included healthy adults, compared at least 2 predefined conditions (non-exercise control (CTRL) and 12 RTx, differentiated by load, sets and/or weekly frequency), and reported muscle strength and/or hypertrophy were included. Analyses Systematic review and Bayesian network meta-analysis methodology was used to compare RTxs and CTRL. Surface under the cumulative ranking curve values were used to rank conditions. Confidence was assessed with threshold analysis. Results The strength network included 178 studies (n=5097; women=45%). The hypertrophy network included 119 studies (n=3364; women=47%). All RTxs were superior to CTRL for muscle strength and hypertrophy. Higher-load (&gt;80% of single repetition maximum) prescriptions maximised strength gains, and all prescriptions comparably promoted muscle hypertrophy. While the calculated effects of many prescriptions were similar, higher-load, multiset, thrice-weekly training (standardised mean difference (95% credible interval); 1.60 (1.38 to 1.82) vs CTRL) was the highest-ranked RTx for strength, and higher-load, multiset, twice-weekly training (0.66 (0.47 to 0.85) vs CTRL) was the highest-ranked RTx for hypertrophy. Threshold analysis demonstrated these results were extremely robust. Conclusion All RTx promoted strength and hypertrophy compared with no exercise. The highest-ranked prescriptions for strength involved higher loads, whereas the highest-ranked prescriptions for hypertrophy included multiple sets. PROSPERO registration number CRD42021259663 and CRD42021258902.
Does a corticosteroid injection plus exercise or exercise alone add to the effect of patient advice and a heel cup for patients with plantar fasciopathy? A randomised clinical trial
Authors: Henrik Riel, Bill Vicenzino, Jens Lykkegaard Olesen, Martin Bach Jensen, Lars Holger Ehlers, Michael Skovdal Rathleff
Journal: British Journal of Sports Medicine (2023)

To compare the effectiveness of patient advice plus heel cup alone (PA) versus PA and lower limb exercise (PAX) versus PAX plus corticosteroid injection (PAXI) to improve self-reported pain in patients with plantar fasciopathy.We recruited 180 adults with plantar fasciopathy confirmed by ultrasonography for this prospectively registered three-armed, randomised, single-blinded superiority trial. Patients were randomly allocated to PA (n=62), PA plus self-dosed lower limb heavy-slow resistance training consisting of heel raises (PAX) (n=59), or PAX plus an ultrasound-guided injection of 1 mL triamcinolone 20 mg/mL (PAXI) (n=59). The primary outcome was changed in the pain domain of the Foot Health Status Questionnaire (ranging from 0 'worst' to 100 'best') from baseline to the 12-week follow-up. The minimal important difference in the pain domain is 14.1 points. The outcome was collected at baseline and at 4, 12, 26, and 52 weeks.The primary analysis found a statistically significant difference between PA and PAXI after 12 weeks favouring PAXI (adjusted mean difference: -9.1 (95% CI -16.8 to -1.3; p=0.023)) and over 52 weeks (adjusted mean difference: -5.2 (95% CI -10.4 to -0.1; p=0.045)). At no follow-up did the mean difference between groups exceed the pre-specified minimal important difference. No statistically significant difference was found between PAX and PAXI or between PA and PAX at any time.No clinically relevant between-group differences were found after 12 weeks. The results indicate that combining a corticosteroid injection with exercise is not superior to exercise or no exercise.NCT03804008.
Treatment of adenoma recurrence after endoscopic mucosal resection
Authors: David J Tate, Lobke Desomer, Maria Eva Argenziano, Neha Mahajan, Mayenaaz Sidhu, Sergei Vosko, Neal Shahidi, Eric Lee, Stephen J Williams, Nicholas G Burgess, Michael J Bourke
Journal: Gut (2023)

Objective Residual or recurrent adenoma (RRA) after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs) of ≥20 mm is a major limitation. Data on outcomes of the endoscopic treatment of recurrence are scarce, and no evidence-based standard exists. We investigated the efficacy of endoscopic retreatment over time in a large prospective cohort. Design Over 139 months, detailed morphological and histological data on consecutive RRA detected after EMR for single LNPCPs at one tertiary endoscopy centre were prospectively recorded during structured surveillance colonoscopy. Endoscopic retreatment was performed on cases with evidence of RRA and was performed predominantly using hot snare resection, cold avulsion forceps with adjuvant snare tip soft coagulation or a combination of the two. Results 213 (14.6%) patients had RRA (168 (78.9%) at first surveillance and 45 (21.1%) thereafter). RRA was commonly 2.5–5.0 mm (48.0%) and unifocal (78.7%). Of 202 (94.8%) cases which had macroscopic evidence of RRA, 194 (96.0%) underwent successful endoscopic therapy and 161 (83.4%) had a subsequent follow-up colonoscopy. Of the latter, endoscopic therapy of recurrence was successful in 149 (92.5%) of 161 in the per-protocol analysis, and 149 (73.8%) of 202 in the intention-to-treat analysis, with a mean of 1.15 (SD 0.36) retreatment sessions. No adverse events were directly attributable to endoscopic therapy. Further RRA after endoscopic therapy was endoscopically treatable in most cases. Overall, only 9 (4.2%, 95% CI 2.2% to 7.8%) of 213 patients with RRA required surgery. Thus 159 (98.8%, 95% CI 95.1% to 99.8%) of 161 cases with initially successful endoscopic treatment of RRA and follow-up remained surgery-free for a median of 13 months (IQR 25.0) of follow-up. Conclusions RRA after EMR of LNPCPs can be effectively treated using simple endoscopic techniques with long-term adenoma remission of &gt;90%; only 16% required retreatment. Therefore, more technically complex, morbid and resource-intensive endoscopic or surgical techniques are required only in selected cases. Trial registration numbers NCT01368289 and NCT02000141
Outcomes following SARS-CoV-2 infection in individuals with and without inflammatory rheumatic diseases: a Danish nationwide cohort study
Authors: Annemarie Lyng Lyng Svensson, Hanne-Dorthe Emborg, Lars Erik Bartels, Torkell Ellingsen, Thomas Adelsten, René Cordtz, Lene Dreyer, Niels Obel
Journal: Annals of the Rheumatic Diseases (2023)

In a setting with an extensive SARS-CoV-2 test strategy and availability of effective vaccines, we aimed to investigate if patients with inflammatory rheumatic diseases (IRD) face greater risk of contracting SARS-CoV-2 and have a worse prognosis of increased risk of hospitalisation, assisted ventilation and death compared with the general population.This was a nationwide, population-based register study that compared outcomes of SARS-CoV-2 infection in Danish patients with IRD (n=66 840) with matched population controls (n=668 400). The study period was from March 2020 to January 2023. Cox regression analyses were used to calculate incidence rate ratios (IRRs) for SARS-CoV-2-related outcomes.We observed a difference in time to first and second positive SARS-CoV-2 test in patients with IRD compared with the general population (IRR 1.06, 95% CI 1.05 to 1.07) and (IRR 1.21, 95% CI 1.15 to 1.27). The risks of hospital contact with COVID-19 and severe COVID-19 were increased in patients with IRD compared with population controls (IRR 2.11, 95% CI 1.99 to 2.23) and (IRR 2.18, 95% CI 1.94 to 2.45). The risks of assisted ventilation (IRR 2.33, 95% CI 1.89 to 2.87) and COVID-19 leading to death were increased (IRR 1.98, 95% CI 1.69 to 2.33). Patients with IRD had more comorbidities compared with the general population. A third SARS-CoV-2 vaccination was associated with a reduced need for hospitalisation with COVID-19 and reduced the risk of death.Patients with IRD have a risk of SARS-CoV-2, which nearly corresponds to the general population but had a substantial increased risk of hospitalisation with COVID-19, severe COVID-19, requiring assisted ventilation and COVID-19 leading to death, especially in patients with comorbidities.
Value of a catch-up HPV test in women aged 65 and above: A Danish population-based nonrandomized intervention study
Authors: Mette Tranberg, Lone Kjeld Petersen, Anne Hammer, Miriam Elfström, Jan Blaakær, Susanne Fogh Jørgensen, Mary Holten Bennetsen, Jørgen Skov Jensen, Berit Andersen
Journal: PLoS Medicine (2023)

High-risk human papillomavirus (HPV) test is replacing cytology as the primary cervical cancer screening test due to superior sensitivity, but in most countries women ≥65 years have never had an HPV test despite they account for around 50% of cervical cancer deaths. We explored the effect of a catch-up HPV test among 65- to 69-year-old women without previous record of HPV-based screening.This population-based nonrandomized intervention study (quasi-experimental design) included Danish women aged 65 to 69 with no record of cervical cancer screening in the last ≥5.5 years and no HPV-exit test at age 60 to 64 at the time of study inclusion. Eligible women residing in the Central Denmark Region were invited for HPV screening either by attending clinician-based sampling or requesting a vaginal self-sampling kit (intervention group, n = 11,192). Women residing in the remaining four Danish regions received standard care which was the opportunity to have a cervical cytology collected for whatever reason (reference group, n = 33,387). Main outcome measures were detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) per 1,000 women eligible for the screening offer and the benefit-harm ratio of the intervention and standard practice measured as the number of colposcopies needed to detect one CIN2+ case. The minimum follow-up time was 13 months for all tested women (range: 13 to 25 months). In the intervention group, 6,965 (62.2%) were screened within 12 months from the date of study inclusion and 743 (2.2%) women had a cervical cytology collected in the reference group. The CIN2+ detection was significantly higher in the intervention group (3.9, 95% confidence interval (CI): [2.9, 5.3]; p < 0.001; n = 44/11,192) as compared to the reference group (0.3, 95% CI: [0.2, 0.6]; n = 11/33,387). For the benefit-harm ratio, 11.6 (95% CI: [8.5, 15.8]; p = 0.69; n = 511/44) colposcopies were performed to detect one CIN2+ in the intervention group as compared to 10.1 (95% CI: [5.4, 18.8]; n = 111/11) colposcopies in the reference group. The study design entails a risk of confounding due to the lack of randomization.The higher CIN2+ detection per 1,000 eligible women in the intervention group supports that a catch-up HPV test could potentially improve cervical cancer prevention in older women. This study informs the current scientific debate as to whether women aged 65 and above should be offered a catch-up HPV test if they never had an HPV test.ClinicalTrials.gov NCT04114968.
The characteristics of patients with <scp>COVID</scp>‐19–associated pediatric vasculitis: an international, multicenter Study: comment on the article by Batu et al
Authors: Nina Emeršič, Tadej Avčin
Journal: Arthritis & Rheumatology (2023)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Author correction to ‘Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice’ [Acta Pharmaceutica Sinica B 13 (2023) 1164–1179]
Authors: Xiaoqing Fan, Chutian Mai, Ling Zuo, Jumin Huang, Chun Xie, Zebo Jiang, Runze Li, Xiaojun Yao, Xingxing Fan, Qibiao Wu, Peiyu Yan, Liang Liu, Jianxin Chen, Ying Xie, Elaine Lai-Han Leung
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2022.10.016.].
Integrating Smoking Cessation Into Low-Dose Computed Tomography Lung Cancer Screening: Results of the Ontario, Canada Pilot
Authors: William K. Evans, Martin C. Tammemägi, Meghan J. Walker, Erin Cameron, Yvonne W. Leung, Sara Ashton, Julie de Loë, Wanda Doyle, Chantal Bornais, Ellen Allie, Koop Alkema, Caroline A. Bravo, Caitlin McGarry, Michelle Rey, Rebecca Truscott, Gail Darling, Linda Rabeneck
Journal: Journal of Thoracic Oncology (2023)